Lipid-water interactions involved in membrane biofunctions

• Project/Area Number: 26560448
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Chemical biology
• Research Institution: Osaka University
• Principal Investigator: Murata Michio 大阪大学, 理学(系)研究科(研究院), 教授 (40183652)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 配座解析 / 分子運動 / 疎水性相互作用 / 脂質二重膜 / 脂肪酸 / 結合タンパク質 / 脂肪酸結合タンパク質 / 疎水分子の水和 / 膜タンパク質 / 周辺脂質 / 分子認識機構

Outline of Final Research Achievements

Cell membranes consist of lipids and proteins, where lipid-lipid and lipid-protein interactions in the aqueous environment plays essential roles in various cellular events. Hydrophobic interactions are known to be essential for the molecular recognitions responsible for stabilization of membrane proteins. In this project, the role of water molecules in lipid-protein interactions was investigated using calorimetry, X-ray crystallography, and molecular simulations. The results clearly show that water molecules in the binding pocket of fatty acid is stabilized by hydrogen-bond network between water and sidechains and thus, changes in sidechain residues do not lead to the significant movement of the bound ligand and water molecules.

Research Products

• [Journal Article] Development of protein seed crystals reinforced by high-strength hydrogels (2015)
  • Author(s): Shigeru Sugiyama, Noriko Shimizu, Keisuke Kakinouchi, Osamu Hiraoka, Hiroyoshi Matsumura, Hiroshi Y. Yoshikawa, Yoshinori Takahashi, Mihoko Maruyama, Masashi Yoshimura, Hiroaki Adachi, Kazufumi Takano, Satoshi Murakami, Tsuyoshi Inoue, Michio Murata, and Yusuke Mori
  • Journal Title: CrystEngComm Volume: 17 Issue: 42 Pages: 8064-8071
  • DOI: 10.1039/c5ce00844a
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Molecular Dynamics Simulations of Heart-type Fatty Acid-binding Protein in Apo and Holo Forms, and Hydration Structure Analyses in the Binding Cavity. (2015)
  • Author(s): Daisuke Matsuoka, Shigeru Sugiyama, Michio Murata, Shigeru Matsuoka*
  • Journal Title: J. Phys. Chem. B Volume: 119 Issue: 1 Pages: 114-127
  • DOI: 10.1021/jp510384f
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Grease matrix as a versatile carrier of proteins for serial crystallography. (2015)
  • Author(s): Sugahara M, Shimamura T, et al.
  • Journal Title: Nat Methods. Volume: 12 Issue: 1 Pages: 61-63
  • DOI: 10.1038/nmeth.3172
  • NAID: 120005682565
  • Peer Reviewed
• [Journal Article] Crystallization and preliminary crystallographic studies of PotA, a membrane-associated ATPase of the spermidine-preferential uptake system in Thermotoga maritime. (2014)
  • Author(s): Sugiyama, S. et al.
  • Journal Title: Acta Crystallogr. F Struct. Biol. Commun. Volume: 70 Issue: 6 Pages: 738-741
  • DOI: 10.1107/s2053230x14008607
  • Peer Reviewed
• [Journal Article] Interaction kinetics of liposome-incorporated unsaturated fatty acids with fatty acid-binding protein 3 by surface plasmon resonance (2014)
  • Author(s): Maria Carmen Tan, Shigeru Matsuoka, Hikaru Ano, Hanako Ishida, Mika Hirose, Fuminori Sato, Shigeru Sugiyama, Michio Murata
  • Journal Title: Bioorganic & Medicinal Chemistry Volume: 22 Issue: 6 Pages: 1804-8
  • DOI: 10.1016/j.bmc.2014.02.001
  • Peer Reviewed
• [Presentation] 創薬加速に向けた難溶性低分子複合体結晶作製の革新的技術開発 (2015)
  • Author(s): 杉山成,垣之内啓介・石田英子・松村浩由・安達宏昭・高野和文・丸山美帆子・吉川洋史・高橋義典・吉村政志・村上 聡・井上 豪・村田道雄・森 勇介
  • Organizer: 第64回高分子討論会
  • Place of Presentation: 神奈川
  • Year and Date: 2015-09-14
• [Presentation] 広範な結晶化条件に適応した新規凝固ゲル中結晶化法 (2015)
  • Author(s): 杉山成,垣之内啓介, 高野和文, 村上聡, 安達宏昭, 丸山美帆子, 吉川洋史, 高橋義典, 吉村政志, 松村浩由, 井上豪, 村田道雄, 森勇介
  • Organizer: 第15回日本蛋白質科学会年会
  • Place of Presentation: 徳島
  • Year and Date: 2015-06-24
• [Presentation] 膜タンパク質研究基盤の構築に向けた合成リン脂質の利用 (2015)
  • Author(s): 杉山成,斎木悠, 島田真典, 垣ノ内啓介, 新山真由美, 花島慎弥, 溝端栄一, 井上豪, 松森信明, 村田道雄
  • Organizer: 第15回日本蛋白質科学会年会
  • Place of Presentation: 徳島
  • Year and Date: 2015-06-24
• [Presentation] 抗原提示タンパク質CD1d と脂質の精密相互作用解析を目指したα-ガラクトシルセラミド標識体の合成 (2014)
  • Author(s): 花島慎弥, 野村拓人, 芝田悠大, 土川博史, 村田道雄, 前仲勝実
  • Organizer: 日本ケミカルバイオロジー学会
  • Place of Presentation: 大阪
  • Year and Date: 2014-06-11 – 2014-06-13
• [Remarks] 村田研究室ＨＰ
  • URL: http://www.chem.sci.osaka-u.ac.jp/lab/murata/